Methods using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for treatment of certain leukemias

Abstract

Methods of treating, preventing or managing leukemias are disclosed. The methods encompass the administration of an immunomodulatory compound of the invention known as Revlimid® or lenalidomide. The invention further relates to methods of treatment using this compound with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods of the invention are also disclosed.

What is claimed is: 
     
       1. A method of treating leukemia, which comprises administering to a patient having leukemia escalating doses of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein a starting dose is between about 1 mg per day and about 10 mg per day, and a maximum dose is between about 10 mg per day wherein the 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof is administered for 21 days followed by seven days rest in a 28 day cycle, and wherein the leukemia is chronic lymphocytic leukemia. 
     
     
       2. The method of  claim 1 , wherein the leukemia is relapsed, refractory, or relapsed and refractory to conventional therapy. 
     
     
       3. The method of  claim 1 , wherein the patient has received prior therapy for chronic lymphocytic leukemia and has demonstrated progression on prior therapy. 
     
     
       4. The method of  claim 1 , wherein the patient has not received prior therapy for chronic lymphocytic leukemia. 
     
     
       5. The method of  claim 1 , wherein the starting dose is about 2.5 mg per day. 
     
     
       6. The method of  claim 1 , wherein the starting dose is about 5 mg per day. 
     
     
       7. The method of  claim 1 , wherein the starting dose is about 10 mg per day. 
     
     
       8. The method of  claim 1 , wherein the maximum dose is about 25 mg per day. 
     
     
       9. The method of  claim 1 , wherein the maximum dose is about 20 mg per day. 
     
     
       10. The method of  claim 1 , wherein the maximum dose is about 15 mg per day. 
     
     
       11. The method of  claim 1 , wherein the maximum dose is about 10 mg per day. 
     
     
       12. The method of  claim 1 , wherein the 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered in an amount of about 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg or 25 mg per day. 
     
     
       13. The method of  claim 1 , wherein the 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered orally. 
     
     
       14. The method of  claim 1 , wherein the 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered in the form of a capsule or tablet. 
     
     
       15. The method of  claim 14 , wherein the 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered in the capsule of an amount of about 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg or 25 mg. 
     
     
       16. The method of  claim 14 , wherein the capsule comprises the 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, lactose anhydrous, microcrystalline cellulose, croscarmellose sodium and magnesium stearate. 
     
     
       17. The method of  claim 1 , wherein the starting dose of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is escalated each week. 
     
     
       18. The method of  claim 1 , wherein the starting dose of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is escalated every 28 days. 
     
     
       19. The method of  claim 1 , further comprising administering a therapeutically effective amount of a second active agent. 
     
     
       20. The method of  claim 19 , wherein the second active agent is an antibody, hematopoietic growth factor, cytokine, anti-cancer agent, antibiotic, cox-2 inhibitor, immunomodulatory agent, immunosuppressive agent, or corticosteroid. 
     
     
       21. The method of  claim 19 , wherein the second active agent is rituximab, fludarabine, cytarabine, dexamethasone, prednisone, or a combination thereof. 
     
     
       22. The method of  claim 21 , wherein the rituximab is administered in an amount of about 375 mg/m 2 . 
     
     
       23. A method of treating leukemia, which comprises administering to a patient having leukemia about 2.5 mg, 5 mg, 10 mg, 15 mg or 20 mg per day of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof for 21 days followed by seven days rest in a 28 day cycle, wherein the leukemia is chronic lymphocytic leukemia. 
     
     
       24. The method of  claim 23 , wherein the leukemia is relapsed, refractory, or relapsed and refractory to conventional therapy. 
     
     
       25. The method of  claim 23 , wherein the patient has received prior therapy for chronic lymphocytic leukemia and has demonstrated progression on prior therapy. 
     
     
       26. The method of  claim 23 , wherein the patient has not received prior therapy for chronic lymphocytic leukemia.